We performed gene therapy to induce expression of GDNF in the ventral tegmental area of rhesus monkey brains. Our approach countered the hypodopaminergic state that is associated with chronic alcohol drinking and reduced alcohol intake to fewer than two drinks per day while other ingestive behaviors remained intact. These findings, along with results from our ongoing clinical trials of GDNF gene therapy in other diseases, support future application of this approach in humans with alcohol-use disorder.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Siciliano, C. A. et al. Cross-species alterations in synaptic dopamine regulation after chronic alcohol exposure. Handb. Exp. Pharmacol. 248, 213–238 (2018). A review article about how presynaptic adaptations result in hypodopaminergic tone in the nucleus accumbens in the rhesus monkey model of alcohol self-administration.
Baker, E. J., Farro, J., Gonzales, S., Helms, C. & Grant, K. A. Chronic alcohol self-administration in monkeys shows long-term quantity/frequency categorical stability. Alcohol Clin. Exp. Res. 38, 2835–2843 (2014). A paper outlining the stability of alcohol self-administration in the rhesus macaque model of AUD.
Barak, S., Ahmadiantehrani, S., Logrip, M. L. & Ron, D. GDNF and alcohol use disorder. Addiction Biology 24, 335–343 (2019). A review article describing the role of GDNF signaling in AUD.
Pearson, T. S. et al. Gene therapy for aromatic l-amino acid decarboxylase deficiency by MR-guided direct delivery of AAV2-AADC to midbrain dopaminergic neurons. Nat. Commun. 12, 4251 (2021). A paper describing the safety and efficacy of MR-guided delivery of AAV2-AADC into the substantia nigra and VTA in children with AADC deficiency.
Heiss, J. D. et al. Trial of magnetic resonance-guided putaminal gene therapy for advanced Parkinson’s disease. Mov. Disord. 34, 1073–1078 (2019). A paper describing the safety of MR-guided delivery of AAV2-GDNF into the putamen in patients with Parkinson’s disease.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This is a summary of: Ford, M. M. et al. GDNF gene therapy for alcohol use disorder in male non-human primates. Nat. Med. https://doi.org/10.1038/s41591-023-02463-9 (2023).
Rights and permissions
About this article
Cite this article
Gene therapy for alcohol-use disorder. Nat Med 29, 1914–1915 (2023). https://doi.org/10.1038/s41591-023-02470-w
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41591-023-02470-w
